Palladium-Catalyzed Carbonylative Reaction: Synthesis Of Benzopolycyclic Compounds

Benzopolycyclic is a common chemical structure.and it is the core skeleton of many natural products and chemicals.They have good biological activity and high application value.For example,Melokhanine E is a typical benzopolycyclic compound with strong antibacterial activity.The benzopolycyclic skeleton in the structure of Taiwaniaquinol B is also the key to its anti-cancer and anti-leukemia effects.Diamine is a main bioactive component isolated from the root bark of Rutaceae plant Dictamnus dasycarpus Turcz,and its key skeleton is benzopolycyclic,which shows many beneficial pharmacological activities.Pteleine shows moderate antibacterial activity against gram-positive pathogens such as Staphylococcus aureus.Therefore,in the field of medicinal chemistry and organic synthesis,the synthesis of benzopolycyclic compounds is of great significance.In the synthesis of benzopolycyclic compounds,transition metals catalyzed carbonylative reaction is a concise and efficient reaction.Based on our group’s long-term research on carbonylation,a series of complex benzopolycyclic compounds,such as indole[1,2-b]isoquinoline compounds,indanone compounds and furoquinoline compounds,were synthesized by using transition metal palladium as catalyst in this thesis.The first part is palladium-catalyzed carbonylative reaction to synthesis indolo[1,2?b]isoquinolines condensed polycyclic compounds.Indolo[1,2-b]isoquinoline compounds with 6/5/6/6 tetracyclic skeleton were synthesized by carbonylation with 2-bromo-N-（2-iodophenyl）benzamide derivatives and phenylacetylene derivatives as the substrate and Pd₂（dba）₃ as the catalyst for the first time.Three C-C bonds and one C-N bond were established by one-step conversion,which provided a new method for the synthesis of indole-[1,2-b]isoquinoline derivatives.The second part is palladium-catalyzed dicarbonylation ofα?Iodo-substituted alkylidenecyclopropanes to synthesis carbamoyl substituted indenones.In this reaction,α-iodine substituted alkylidenecyclopropanes derivatives and amine compounds were used as substrates,and Pd Cl₂ was used as catalyst to realize the dicarbonylation of alkylidenecyclopropanes for the first time.Two carbonyl groups were added to the product through the cleavage of carbon-carbon bonds at the proximal end,and a series of carbamoyl substituted indanone compounds were prepared efficiently.Notably,the several amino acid derivatives,natural products and drugs are also suitable for this kind of dicarbonylation reaction,which further emphasizes the application prospect of this reaction.The third part is palladium/copper-catalyzed carbonylation ofα-aminoaryl-tethered alkylidenecyclopropanes:synthesis of furoquinoline derivatives.This reaction were usedα-aminoaryl-tethered alkylidenecyclopropanes derivatives as substrate.Under the co-catalysis of Pd Cl₂ and Cu Br₂,oxygen was used as the terminal oxidant in this reaction.A range of furoquinoline derivatives were efficiently prepared in good to excellent yields via the incorporation of a carbonyl group into the product with the cleavage of the proximal C–C bond of the ACPs.